Acute dose-dependent effects of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) compared with 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin in a double-blind, placebo-controlled study in healthy participants.

Arikci D, Borgulya J, Straumann I, Vizeli P, Luethi D, Thomann J, Rudin D, Vukalovic I, Eckert A, Liechti ME, Holze F

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology28 Apr 2026Cited by 2 (Europe PMC)

PMID42049943PMCIDPMC13291353DOI10.1038/s41386-026-02428-9PepBankPUB-42049943

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Summary

Based on its in vitro profile and preliminary evidence, 4-bromo-2,5-dimethoxyphenethylamine (2C-B) may have psychoactive properties that are similar to 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin, which are investigated for the treatment of posttraumatic stress disorder and depressive disorders. We compared acute effects of 2C-B (10, 20, and 30 mg), 125 mg MDMA, and 25 mg psilocybin in 24 healthy participants (12 women, 12 men) using a double-blind, randomized, placebo-controlled, crossover design. Outcome measures included acute subjective effects, autonomic effects, adverse effects, effects on emotional and cognitive empathy, plasma oxytocin and neurophysin I concentrations, and pharmacokinetics up to 9 h. 2C-B produced dose-dependent subjective effects, with the 30 mg dose exerting comparable "any drug effects" to MDMA but lower "any drug effects" than psilocybin. Only psilocybin induced "bad drug effects" and "anxiety" compared with placebo. The 30 mg dose of 2C-B induced psychedelic-type alterations of state of consciousness and increased emotional empathy similarly to MDMA. The average subjective effect duration of 30 mg 2C-B was 4.9 h and similar to MDMA (4.8 h) and shorter than psilocybin (6.1 h). MDMA produced the highest cardiovascular stimulation, followed by psilocybin and 2C-B. Only MDMA increased plasma oxytocin and neurophysin I concentrations. 2C-B exhibited dose-proportional pharmacokinetics, with a plasma elimination half-life of ~1.3 h. The 30 mg dose of 2C-B induced entactogenic and psychedelic effects similarly to MDMA and psilocybin, respectively. MDMA is more cardiostimulant than psilocybin and 2C-B. At the tested dose-level, psilocybin is more distressing than MDMA and 2C-B. These results may assist with dose-finding for future 2C-B research and provide a direct comparison with standard doses of the prototypical compounds MDMA and psilocybin. Trial registration: ClinicalTrials.gov identifier: NCT05523401.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

No result from this study comes from a test of the peptide.

Natural levels measured3

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

01HumanEndogenous levelRandomized controlled trialOther
In healthy participants, MDMA increased plasma oxytocin concentrations versus placebo.
In plain wordsIn healthy people, MDMA raised the body's own oxytocin levels in blood compared with placebo.
Peptide
Oxytocin
Outcome
IncreasePlasma oxytocin after MDMA
Study
n = 24
Comparator
Placebo
Outcome group
Endogenous peptide levels · Endocrine and hormones
Source sentences
Summary
Only MDMA increased plasma oxytocin and neurophysin I concentrations.
2 context sentences(design, population, supporting numbers)
Summary · context
Outcome measures included acute subjective effects, autonomic effects, adverse effects, effects on emotional and cognitive empathy, plasma oxytocin and neurophysin I concentrations, and pharmacokinetics up to 9 h.
Summary · context
We compared acute effects of 2C-B (10, 20, and 30 mg), 125 mg MDMA, and 25 mg psilocybin in 24 healthy participants (12 women, 12 men) using a double-blind, randomized, placebo-controlled, crossover design.
This result measures the body's own Oxytocin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4204994301
02HumanEndogenous levelRandomized controlled trialOther
In healthy participants, 2C-B did not increase plasma oxytocin concentrations versus placebo; only MDMA did.
In plain wordsIn healthy people, 2C-B did not change the body's own oxytocin levels in blood compared with placebo.
Peptide
Oxytocin
Outcome
No significant changePlasma oxytocin after 2C-B
Study
n = 24
Comparator
Placebo
Outcome group
Endogenous peptide levels · Endocrine and hormones
Source sentences
Summary
Only MDMA increased plasma oxytocin and neurophysin I concentrations.
2 context sentences(design, population, supporting numbers)
Summary · context
Outcome measures included acute subjective effects, autonomic effects, adverse effects, effects on emotional and cognitive empathy, plasma oxytocin and neurophysin I concentrations, and pharmacokinetics up to 9 h.
Summary · context
We compared acute effects of 2C-B (10, 20, and 30 mg), 125 mg MDMA, and 25 mg psilocybin in 24 healthy participants (12 women, 12 men) using a double-blind, randomized, placebo-controlled, crossover design.
This result measures the body's own Oxytocin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4204994302
03HumanEndogenous levelRandomized controlled trialOther
In healthy participants, psilocybin did not increase plasma oxytocin concentrations versus placebo; only MDMA did.
In plain wordsIn healthy people, psilocybin did not change the body's own oxytocin levels in blood compared with placebo.
Peptide
Oxytocin
Outcome
No significant changePlasma oxytocin after psilocybin
Study
n = 24
Comparator
Placebo
Outcome group
Endogenous peptide levels · Endocrine and hormones
Source sentences
Summary
Only MDMA increased plasma oxytocin and neurophysin I concentrations.
2 context sentences(design, population, supporting numbers)
Summary · context
Outcome measures included acute subjective effects, autonomic effects, adverse effects, effects on emotional and cognitive empathy, plasma oxytocin and neurophysin I concentrations, and pharmacokinetics up to 9 h.
Summary · context
We compared acute effects of 2C-B (10, 20, and 30 mg), 125 mg MDMA, and 25 mg psilocybin in 24 healthy participants (12 women, 12 men) using a double-blind, randomized, placebo-controlled, crossover design.
This result measures the body's own Oxytocin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4204994303

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Version history

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Version 2Current
11 Oct 2026, 00:50 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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